Study of Serum Haptoglobin and Its Glycoforms in the Diagnosis of Hepatocellular Carcinoma: A Glycoproteomic Approach

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• 作者：Irene L. Ang ; Terence C. W. Poon ; Paul B. S. Lai ; Anthony T. C. Chan ; Sai-Ming Ngai ; Alex Y. Hui ; Philip J. Johnson ; Joseph J. Y. Sung
• 刊名：Journal of Proteome Research
• 出版年：2006
• 出版时间：October 2006
• 年：2006
• 卷：5
• 期：10
• 页码：2691 - 2700
• 全文大小：370K
• 年卷期：v.5,no.10(October 2006)
• ISSN：1535-3907

文摘

Increased serum haptoglobin concentration and changes in its glycosylation have been reported incertain cancer types. Information for hepatocellular carcinoma (HCC) has not yet been available. Inthis study, we aimed to carry out a systematic analysis of serum concentrations of haptoglobin (Hp)and its glycoforms in the patients with HCC and noncancer patients only with chronic liver diseases(CLD) and to examine their clinical values. This study was divided into two major parts, (1) measurementof serum Hp concentration, and investigation of its value in the diagnosis of HCC, and (2) quantitativeanalysis of Hp glycoforms with alpha-2,6-sialylation and/or alpha-1,6-fucosylation by using lectin affinitypurification and 2D gel electrophoresis and investigation of their relationships with tumor stage. Theconcentrations of serum Hp in HCC patients were significantly higher than those in noncancer patientswith CLD. With the use of serum concentrations of Hp and alpha-fetoprotein, a logistic regression (LR)model was developed from the training data set and used to classify the validation cases. At a specificityof 95%, the sensitivity for HCC detection was 79%. Comparing serum concentrations of alpha-2,6-sialylated Hp (S-Hp) and alpha-1,6-fucosylated Hp (F-Hp) between HCC and CLD patients suggeststhat purification of S-Hp and F-Hp could enrich the glycosylation variants associated with HCC. 2Dgel analysis of S-Hp and F-Hp identified a total of 18 glycoforms. A unique pattern of Hp glycoformscomprising both hypersialylated fucosylated and hyposialylated fucosylated species was found in theHCC patients. Serum concentrations of these glycoproteins were significantly higher in the patientswith advanced tumors, suggesting their tumor-specific nature. We have shown that serum Hp is apotential biomarker in the diagnosis of HCC. The combined use of Hp and AFP could greatly improvethe diagnostic accuracy. A unique pattern of Hp glycoforms with altered sialylation and fucosylation isspecific to HCC and associated tumor progression.